Casper Hoogenraad is a member of “De Jonge Akademie (DJA)”, which is part of the Royal Academy of Arts and Sciences (KNAW). DJA focuses on three themes - interdisciplinarity within science and scholarship, science policy and science and society. See short introduction video (in Dutch). For more information about De Jonge Akademie, please see their website.

Casper Hoogenraad is member of the European Molecular Biology Organization (EMBO) - Young Investigator Program (YIP). EMBO-YIP selects independent scientists throughout their member states, thereby creating a European network of outstanding life scientists. See website EMBO-YIP.

Research summary

The primary goal of the lab is to understand how intracellular protein trafficking underlies neuronal development and function. This work is significant because neurons are dependent upon very precise localization of proteins to support their ability to send and receive information.

Neuronal cells represent a unique model for addressing fundamental questions in molecular and cellular biology. The size, shape and specialized functions of neurons permit analyses of neuronal migration, axon and dendrite outgrowth, and synapse formation and function. By understanding the basic cellular mechanisms and development of individual neurons, we can better understand how the nervous system develops and functions in an entire animal.

We particularly focus on the areas of microtubule cytoskeleton, synaptic cargo trafficking and synaptic plasticity. The research in the lab can roughly be divided in three themes:

Projects

Dendritic spines are small protrusions on neuronal dendrites that constitute the postsynaptic component of most excitatory (glutamatergic) synapses in the brain. Ever since their discovery at the turn of the 19th century by Ramon y Cajal, spines are assumed to serve as determinants of synaptic strength and major sites of information processing and storage in the brain. There is now strong experimental evidence that changes in dendritic spine morphology play an important role in the cognitive processes in brain.

We have recently shown that dynamic microtubules enter dendritic spines, are temporal and spatial regulators of spine actin dynamics and cause transient morphological spine alterations. Now we focus on i) the molecular mechanism by which dynamic microtubules enter dendritic spines and regulate actin dynamics ii) the relation between cytoskeletal organization and cargo transport in spines iii) the effect of synaptic activity on the microtubule cytoskeleton.

- Motor proteins and adaptors as regulators of synaptic transport

In order to form new synapses and alter the strength of synaptic transmission, neurons need a regulatory mechanism to deliver and remove synaptic proteins at synaptic sites. Neurons make use of active transport driven by molecular motor proteins to move synaptic cargo over either microtubules (kinesin, dynein) or actin filaments (myosin) to their specific site of action. These mechanisms are crucial for the initial establishment of synaptic specializations during synaptogenesis and for activity-dependent changes in synaptic strength during plasticity.

Research in the lab focuses on synaptic cargo sorting and trafficking into axons and dendrites and the spatial and temporal regulation of motor protein-based transport. We recently developed an inducible cargo trafficking assay to probe motor protein activity in neuronal cells.

Understanding the molecular link between neuronal transport and synaptic pathology may provide essential insight into the pathogenesis of these disorders, and can reveal novel drug targets to treat these mental and neurological disorders. We focus on the role of the cytoskeleton and neuronal transport routes in several psychiatric and neurological disorders.

Lab members

Technicians:

Phebe Wulf

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Bart de Haan

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Postdocs:

Ines Cunha Ferreira

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Amélie Fréal

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Laura Gumy

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Martin Harterink

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Marina Mikhaylova

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Philipp Schätzle

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Elena Tortosa

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Lena Will

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Harold Mac Gillavry

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Gabi Plucinska

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PhD students:

Kah Wai Yau

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Marta Silva

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Mariella Franker

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Joanna Lipka

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Sam van Beuningen

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Petra van Bergeijk

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Josta Kevenaar

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Catia Frias

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Michael Dumbacher

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Riccardo Stucchi

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Dieudonnée van de Willige

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Cao Yujie

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